Although venous thrombosis is a well described disease entity, the exact pathophysiologic mechanisms of this process have not been elucidated. Progress to date has yielded an ex vivo swine model of venous thrombosis that does not require the use of anticoagulated blood and provides a means for controlling hemodynamic factors such as perfusion pressure and blood flow as they relate to clot formation. The ability to study intravascular clot formation under precisely controlled conditions makes this model an appropriate experimental tool for the study of the mechanisms involved in venous thrombosis. The aims of this proposal are to clarify the mechanisms involved in the production of venous thrombi. Specifically, the goals of the study are: 1) to histologically characterize venous thrombosis as it occurs over time in a de-endothelialized venous segment; 2) to investigate the influence of blood flow rate and perfusion pressure on the development of intravascular thrombus formation; 3) to investigate differences in the character of thrombus formation within various vascular tissues; 4) to determine the relative role of platelets and the coagulation factors in the development of venous thrombosis and 5) to ascertain differences in clot formation in the postoperative and unoperated states, and to investigate the relative role of the blood components and the vessel wall in postoperative venous thrombosis. These experiments will yield information on the importance of various factors involved in venous thrombosis. In addition, the proposed experiments will explore the use of antiplatelet and anticoagulant agents in the modification of the thrombotic prccess. In this way an objective scientific basis may be developed for planning subsequent clinical trials aimed at the prohylaxis of deep venous thrombosis.